Annonaceousacetogenins compounds and preparation method thereof

A kind of technology of annua lactone and compound, which is applied in the field of tetrahydrofuran-containing annua lactone compound and its preparation, and can solve problems such as unsatisfactory performance.

Inactive Publication Date: 2008-04-30

EAST CHINA UNIV OF SCI & TECH

0 Cites 3 Cited by

AI-Extracted Technical Summary

Problems solved by technology

[0006] Although the existing tetrahydrofuran-containing annonaceous lactone compounds (compounds shown in formula...

Abstract

The invention relates to annonaceous acetogenin compound including tetrahydrofuran and the preparation method thereof. The structure of the annonaceous acetogenin compound is shown as the formula A or the formula B. The method to prepare the annonaceous acetogenin compound comprises the main steps that: under the condition of the existence of lithium alkyl, the ring opening coupling reaction is operated through chiral double tetrahydrofuran alkyne compound with a blocking group and chiral epoxy lactone compound with a blocking group to obtain intermediate compound, the deprotection reaction and the electronation reaction are operated in sequence to the intermediate compound to obtain an object. Compared with the prior annonaceous acetogenin compound including the tetrahydrofuran, the antineoplastic activity of the annonaceous acetogenin compound including the tetrahydrofuran prepared by the invention is obviously improved. In the formula A and the formula B, m is 2 to 10, n is 5 to 8.

Application Domain

Organic chemistryAntineoplastic agents

Technology Topic

Lactone CompoundLithium +8

Image

Examples

Experimental program(4)

Example Embodiment

[0021] Example 1

[0022]

[0023] Among them: MOM is CH 2 OCH 3 (The same below)

[0024] Dissolve 0.32mmol of compound 4 in the freshly distilled tetrahydrofuran solution, place it in a low temperature tank at -78℃ and stir for 10-15 minutes, then add 0.15mL of hexane solution with a concentration of 2.5Mn-BuLi dropwise. After the addition is complete, continue Stir for 30 minutes; then drop the tetrahydrofuran solution of compound 5 into the system, continue the reaction for 1 to 2 hours, quench the reaction with saturated ammonia chloride at 0°C, extract with ethyl acetate, and dry with anhydrous sodium sulfate , Concentrated and column chromatography gave the product (compound 3) 143mg, the yield was 55%.

[0025]

[0026] 0.29 mmol of compound 3 is dissolved in a mixture of 0.5-10 ml of methanol, tetrahydrofuran and 6N hydrochloric acid, wherein the volume ratio of 6N hydrochloric acid, tetrahydrofuran and methanol is 1:1:2. After stirring at room temperature for about 16 hours, the reaction was quenched with water, extracted with ethyl acetate, dried, concentrated, and column chromatography was used to obtain 156.3 mg of the product (compound 2) with a yield of 85%.

[0027]

[0028] Mix 0.2mmol of compound 2, 10-15mmol of p-toluenesulfonyl hydrazide and 15ml of dimethoxyethane, heat to reflux, and dropwise add 25-30mmol of sodium acetate and 10-15ml within 3 to 5 hours After the addition is completed, the mixture is cooled to room temperature, poured into 30mL of water, extracted with ether 10mL×3, the organic phases are combined, dried with anhydrous sodium sulfate, concentrated, column chromatography, and the product is obtained. The yield is 70% .

[0029] 1 H-NMR(CDCl 3 , 400MHz) δ: 7.18(q, J=1.5Hz, 1H), 5.09(qq, J=6.8, 1.5Hz, 1H), 4.06(m, 1H), 3.97(m, 1H), 3.85(m, 1H) ), 3.84 (m, 2H), 3.59 (m, 1H), 3.38 (m, 2H), 2.53 (m, 1H), 2.40 (m, 1H), 2.05 (m, 1H), 1.96 (m, 2H) , 1.70-1.1.45 (m, 23H), 0.88 (t, J=7.0 Hz, 3H);

[0030] 13 C-NMR(CDCl 3 , 100MHz) δ: 174.6, 151.9, 131.2, 83.5, 82.6, 81.5, 80.8, 78.2, 74.5, 73.6, 71.7, 70.0, 33.5, 28.8, 28.3, 19.0, 14.1.

Example Embodiment

[0031] Example 2

[0032] The structural formula is The bis-tetrahydrofuran acetylene compound with the structural formula is The chiral epoxy compound is reacted with the same operation as in Example 1, and the following target compound (compound 6) can be obtained:

[0033]

[0034] Structure characterization data of compound 6:

[0035] 1 HNMR(CDCl 3 , 400MHz) δ: 7.18(q, J=1.5Hz, 1H), 5.09(qq, J=6.8, 1.5Hz, 1H), 4.06(m, 1H), 3.97(m, 1H), 3.85(m, 1H) ), 3.84 (m, 2H), 3.59 (m, 1H), 3.38 (m, 2H), 2.53 (m, 1H), 2.40 (ddt, J = 15.2, 8.5, 1.8 Hz), 2.05 (m, 1H) , 1.96 (m, 2H), 1.70-1.45 (m, 23H), 0.88 (t, J=7.0 Hz, 3H);

[0036] 13 CNMR(CDCl 3 , 100MHz): δ174.6, 151.9, 131.2, 83.5, 82.6, 81.5, 80.8, 78.2, 74.5, 73.6, 71.7, 70.0, 33.5, 28.8, 28.3, 19.0, 14.1.

Example Embodiment

[0037] Example 3

[0038] The structural formula is The bis-tetrahydrofuran acetylene compound with the structural formula is or The reaction of the chiral epoxy compound, the operation is the same as that of implementation 1, and the following target compounds (compound 7 and compound 8) can be obtained:

[0039]

[0040] Structure characterization data of compound 7:

[0041] 1 H-NMR(CDCl 3 , 400MHz) δ 7.18 (q, J = 1.5Hz, 1H), 5.09 (qq, J = 6.8, 1.5Hz, 1H), 4.06 (m, 1H), 3.97 (m, 1H), 3.85 (m, 1H) , 3.84 (m, 2H), 3.59 (m, 1H), 3.38 (m, 2H), 2.53 (m, 1H), 2.40 (ddt, J = 15.2, 8.5, 1.8 Hz), 2.05 (m, 1H), 1.96 (m, 2H), 1.70-1.45 (m, 19H), 0.88 (t, J=7.0 Hz, 3H);

[0042] 13 CNMR(CDCl 3, 100MHz): δ174.6, 151.9, 131.2, 83.5, 82.6, 81.5, 80.8, 78.2, 74.5, 73.6, 71.7, 70.0, 43.6, 38.1, 33.5, 28.8, 28.3, 23.0, 19.0, 14.1.

[0043]

[0044] Structure characterization data of compound 8:

[0045] 1 H-NMR(CDCl 3 , 400MHz) δ 7.18 (q, J = 1.5Hz, 1H), 5.09 (qq, J = 6.8, 1.5Hz, 1H), 4.06 (m, 1H), 3.97 (m, 1H), 3.85 (m, 1H) , 3.84 (m, 2H), 3.59 (m, 1H), 3.38 (m, 2H), 2.53 (m, 1H), 2.40 (ddt, J = 15.2, 8.5, 1.8 Hz), 2.05 (m, 1H), 1.96 (m, 2H), 1.70-1.45 (m, 19H), 0.88 (t, J=7.0 Hz, 3H);

[0046] 13 CNMR(CDCl 3 , 100MHz): δ174.6, 151.9, 131.2, 83.5, 82.6, 81.5, 80.8, 78.2, 74.5, 73.6, 71.7, 70.0, 43.6, 38.1, 33.5, 28.8, 28.3, 23.0, 19.0, 14.1.

PUM

Description & Claims & Application Information

We can also present the details of the Description, Claims and Application information to help users get a comprehensive understanding of the technical details of the patent, such as background art, summary of invention, brief description of drawings, description of embodiments, and other original content. On the other hand, users can also determine the specific scope of protection of the technology through the list of claims; as well as understand the changes in the life cycle of the technology with the presentation of the patent timeline. Login to view more.